A Comprehensive Analysis of p16 Expression, Gene Status, and Promoter Hypermethylation In Surgically Resected Non-small Cell Lung Carcinomas

Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Zelger, Bettina; Bihl, Michel; Foerster, Anja; Augustin, Florian; Fiegl, Michael; Savic, Spasenija

doi:10.1097/jto.0b013e3182295745

Cited by 48 publications

(48 citation statements)

References 26 publications

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“…Molecules involved in the cell cycle have often been reported as prognostic markers and although the cell cycle also seems to offer potential anticancer targets, such strategies are not yet routinely established [34,35,36,37]. This review summarizes the importance and recent findings concerning the cell cycle in NSCLC and discusses the prognostic and predictive aspects as well as the challenge of therapeutic approaches.…”

Section: Symptoms Prognosis and Managementmentioning

confidence: 99%

“…Furthermore, cyclin D1 overexpression correlated with p16 loss and RB inactivation and the overall survival of patients with the combination of cyclin D1 overexpression and loss of p16 tended to show a rapid decline [59]. Our own observations of a multitude of cell cycle markers in a comparably large cohort (405 cases) of surgically resected NSCLC revealed that cyclin D1 overexpression is associated with the overexpression of cyclin D3, p27 (nuclear), p21 and the loss of p16 [36,37]. The only independent prognostic parameters by multivariable analysis were the overexpression of cyclin D1 and the loss of p16, both indicating poor overall survival [36,37].…”

Section: Cyclins In Nsclcmentioning

confidence: 99%

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Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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Non-small-cell lung cancer (NSCLC) is among the most frequently diagnosed malignancy and a leading cause for cancer mortality worldwide. Despite various efforts, practical prognostic and predictive markers are still few. We review recent findings concerning the cell cycle in NSCLC and discuss prognostic and predictive aspects as well as the challenge of targeted therapeutic approaches. Deregulation of the cell cycle is a common event in NSCLC. Usually, several defects of cell cycle regulation are concomitant and have a cumulative adverse effect on prognosis. Therefore, analysis of a variety of interacting molecules is desirable for adequate deductions. Immunohistochemical interpretations should include the subcellular staining localization, since this can reflect the functional properties of a protein. Overexpression of cyclins, especially D-type cyclins, has repeatedly been associated with poor prognosis in NSCLC. Predictive data is less conclusive; however, loss of the expression of cyclin-dependent kinase inhibitors seems to correlate with sensitivity to antiproliferative drugs. Various inhibitors of Aurora kinases are currently being evaluated regarding their potential as targeted therapies in NSCLC. In conclusion, the cell cycle offers several prognostic, predictive and therapeutic possibilities in NSCLC, many still developmental. Progress in this field has the potential to improve the current scenario for NSCLC patients.

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Section: Symptoms Prognosis and Managementmentioning

confidence: 99%

Section: Cyclins In Nsclcmentioning

confidence: 99%

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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“…63 Several genes that have been identifi ed, including CDKN2A , FHIT , APC , p16 , and RASSF1A , appear to be commonly methylated. [64][65][66][67] Methylated genes may be detected using several techniques. The majority of early studies used technologies such as methylation-specifi c PCR and restriction landmark genomic scanning, which are targeted to specifi c genomic regions and candidates.…”

Section: Methylationmentioning

confidence: 99%

Molecular Biology of Lung Cancer

Nana‐Sinkam

Powell

2013

Chest

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Lung cancer is the leading cause of cancer death in the United States, with 157,000 deaths annually, and in the world, with 1,375,000 deaths annually. 2 The overall 5-year survival for lung cancer remains at 16%, which is signifi cantly lower than the mortality rate for other common cancers, including colon, breast, and prostate cancer. The discrepancy in the mortality rate of lung cancer compared with other cancers has several explanations. First, lung cancers are typically detected at an advanced stage. The anticipated implementation of population-based screening for lung cancer is expected to decrease mortality. Second, compared with the other common cancers that share adenocarcinoma as the histology, lung cancer is heterogenous histologically and biologically. Until recently, lung cancer was treated as a homogenous disease with all nonsmall cell lung cancers (NSCLCs) treated identically, solely on the basis of clinical stage. Based on bench and clinical research, the treatment of lung cancer has been refi ned, with treatments allocated according to histology and specifi c molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) has been particularly successful as a treatment modality, demonstrating response rates in patients with EGFR-mutated adenocarcinoma that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, Based on recent bench and clinical research, the treatment of lung cancer has been refi ned, with treatments allocated according to histology and specifi c molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are signifi cantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and fi eld molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutat...

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“…Повышенная экспрессия HDACs может привести к глушению транскрипции генов и аберрантной транскрипции из-за измененной экспрессии / мутации генов, кодирующих гистонаце-тилтрансферазу (HAT), HDAC-ферменты или их свя-зывающих партнеров, и тесно сопряжена с канцеро-генезом. Это происходит при многих злокачественных опухолях у человека, указывая на то, что активность аберрантного эпигенетического ацетилирования свя-зана с развитием рака [44][45][46]. Полагают, что после-довательные стадии ЭМП и мезенхимально-эпители-ального перехода, происходящие в процессе опухолевой прогрессии, могут быть обратимыми и свя-заны с эпигенетическими изменениями.…”

Section: экспериментальные статьиunclassified

The transforming growth factor beta-1 in the oncogenesis of human lung adenocarcinoma

et al. 2017

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A Comprehensive Analysis of p16 Expression, Gene Status, and Promoter Hypermethylation In Surgically Resected Non-small Cell Lung Carcinomas

Cited by 48 publications

References 26 publications

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Molecular Biology of Lung Cancer

The transforming growth factor beta-1 in the oncogenesis of human lung adenocarcinoma

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